Tissue adhesives have many potential medical applications, including wound closure, supplementing or replacing sutures or staples in internal surgical procedures, adhesion of synthetic onlays or inlays to the cornea, drug delivery devices, anti-adhesion barriers to prevent post-surgical adhesions, and as a hemostatic sealant. Conventional tissue adhesives are generally not suitable for a wide range of adhesive applications. For example, cyanoacrylate-based adhesives have been used for topical wound closure, but the release of toxic degradation products limits their use for internal applications. Fibrin-based adhesives are slow curing, have poor mechanical strength, and pose a risk of viral infection. Additionally, the fibrin-based adhesives do not bond covalently to the underlying tissue.
Several types of hydrogel tissue adhesives have been developed which have improved adhesive and cohesive properties and are nontoxic. These hydrogels are generally formed by reacting a component having nucleophilic groups with a component having electrophilic groups, which are capable of reacting with the nucleophilic groups of the first component to form a crosslinked network via covalent bonding. However, these hydrogels typically swell or dissolve away too quickly, or lack sufficient adhesion or mechanical strength, thereby decreasing their effectiveness as surgical adhesives.
Kodokian et al. (copending and commonly owned U.S. Patent Application Publication No. 2006/0078536) describe hydrogel tissue adhesives formed by reacting an oxidized polysaccharide with a water-dispersible, multi-arm polyether amine. These adhesives provide improved adhesion and cohesion properties, crosslink readily at body temperature, maintain dimensional stability initially, do not degrade rapidly, and are nontoxic to cells and non-inflammatory to tissue.
It is known that hydrogel tissue adhesives may be formed by mixing two aqueous solutions, each of which contains one of the crosslinkable components. The two solutions can be premixed using a mixing device before application to the desired site or can be applied separately and allowed to mix at the site of application. Additionally, the use of dried hydrogels and dried hydrogel precursors has been described (see for example, Rhee et al. U.S. Pat. No. 5,874,500, Sawhney et al., U.S. Pat. No. 6,703,047, and Odermatt et al., U.S. Patent Application Publication No. 2006/0134185). However, for some applications, for example a hemostatic sealant, it may be advantageous to have the tissue adhesive in a fibrous form which would be more effective in absorbing blood to help control bleeding and thereby having an easier application.